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International Maritime Health 2019The authors present a short summary of the current state of malaria vaccine development and the per- spectives for the availability of a malaria vaccines for travellers...
The authors present a short summary of the current state of malaria vaccine development and the per- spectives for the availability of a malaria vaccines for travellers from non-endemic countries. There is currently no commercially available malaria vaccine for travellers. The efficacy of the RTS,S/AS01 vaccine is limited and differs dramatically from the effects of other vaccines administered in travel medicine. In the current recommendations, the use of repellents is deemed the most important measure to prevent malaria infection, and in the high-risk destinations, chemoprophylaxis is strongly advised. Many questions in malaria vaccinology remain unanswered.
Topics: Humans; Malaria; Malaria Vaccines; Plasmodium; Travel-Related Illness
PubMed: 30931520
DOI: 10.5603/IMH.2019.0010 -
Frontiers in Cellular and Infection... 2021is an obligate intracellular parasite, which is responsible for a widely distributed zoonosis. Effective vaccines against toxoplasmosis are necessary to protect the...
is an obligate intracellular parasite, which is responsible for a widely distributed zoonosis. Effective vaccines against toxoplasmosis are necessary to protect the public health. The aim of this study is to evaluate the immune efficacy of DNA vaccines encoding TgMIC5 and TgMIC16 genes against infection. The recombinant plasmid pVAX-MIC5 and pVAX-MIC16 were constructed and injected intramuscularly in mice. The specific immune responses and protection against challenge with RH tachyzoites were evaluated by measuring the cytokine levels, serum antibody concentrations, lymphocyte proliferation, lymphocyte populations, and the survival time. The protection against challenge with the RH tchyzoites and PRU cysts was examined by evaluation of the reduction in the brain cyst burden. The results indicated that immunized mice showed significantly increased levels of IgG, IFN-γ, IL-2, IL-12p70, and IL-12p40 and percentages of CD4 and CD8 T cells. Additionally, vaccination prolonged the mouse survival time and reduced brain cysts compared with controls. Mouse groups immunized with a two-gene cocktail of pVAX-MIC5 + pVAX-MIC16 were more protected than mouse groups immunized with a single gene of pVAX-MIC5 or pVAX-MIC16. These results demonstrate that TgMIC5 and TgMIC16 induce effective immunity against toxoplasmosis and may serve as a good vaccine candidate against infection.
Topics: Animals; Antibodies, Protozoan; CD8-Positive T-Lymphocytes; Cytokines; Immunity, Cellular; Mice; Protozoan Proteins; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccines, DNA
PubMed: 34595126
DOI: 10.3389/fcimb.2021.686004 -
Frontiers in Immunology 2022Cheap, easy-to-produce oral vaccines are needed for control of coccidiosis in chickens to reduce the impact of this disease on welfare and economic performance. yeast...
Cheap, easy-to-produce oral vaccines are needed for control of coccidiosis in chickens to reduce the impact of this disease on welfare and economic performance. yeast expressing three antigens were developed and delivered as heat-killed, freeze-dried whole yeast oral vaccines to chickens in four separate studies. After vaccination, replication was reduced following low dose challenge (250 oocysts) in Hy-Line Brown layer chickens (p<0.01). Similarly, caecal lesion score was reduced in Hy-Line Brown layer chickens vaccinated using a mixture of S. cerevisiae expressing EtAMA1, EtIMP1 and EtMIC3 following pathogenic-level challenge (4,000 oocysts; p<0.01). Mean body weight gain post-challenge with 15,000 oocysts was significantly increased in vaccinated Cobb500 broiler chickens compared to mock-vaccinated controls (p<0.01). Thus, inactivated recombinant yeast vaccines offer cost-effective and scalable opportunities for control of coccidiosis, with relevance to broiler production and chickens reared in low-and middle-income countries (LMICs).
Topics: Animals; Chickens; Coccidiosis; Eimeria tenella; Female; Male; Poultry Diseases; Protozoan Proteins; Protozoan Vaccines; Saccharomyces cerevisiae; Vaccination; Vaccines, Subunit
PubMed: 35185896
DOI: 10.3389/fimmu.2022.809711 -
The Journal of Clinical Investigation Apr 2024BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial.RESULTSThe vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).
Topics: Adult; Humans; Malaria Vaccines; Plasmodium falciparum; Protozoan Proteins; Adjuvants, Immunologic; Antigens, Protozoan; Aluminum Hydroxide; Antibodies, Protozoan; Malaria; Malaria, Falciparum
PubMed: 38290009
DOI: 10.1172/JCI175707 -
Nature Communications Oct 2022Defining mechanisms of pathogen immune evasion and neutralization are critical to develop potent vaccines and therapies. Merozoite Surface Protein 1 (MSP-1) is a malaria...
Defining mechanisms of pathogen immune evasion and neutralization are critical to develop potent vaccines and therapies. Merozoite Surface Protein 1 (MSP-1) is a malaria vaccine antigen and antibodies to MSP-1 are associated with protection from disease. However, MSP-1-based vaccines performed poorly in clinical trials in part due to a limited understanding of the protective antibody response to MSP-1 and of immune evasion by antigenic diversion. Antigenic diversion was identified as a mechanism wherein parasite neutralization by a MSP-1-specific rodent antibody was disrupted by MSP-1-specific non-inhibitory blocking/interfering antibodies. Here, we investigated a panel of MSP-1-specific naturally acquired human monoclonal antibodies (hmAbs). Structures of multiple hmAbs with diverse neutralizing potential in complex with MSP-1 revealed the epitope of a potent strain-transcending hmAb. This neutralizing epitope overlaps with the epitopes of high-affinity non-neutralizing hmAbs. Strikingly, the non-neutralizing hmAbs outcompete the neutralizing hmAb enabling parasite survival. These findings demonstrate the structural and mechanistic basis for a generalizable pathogen immune evasion mechanism through neutralizing and interfering human antibodies elicited by antigenic diversion, and provides insights required to develop potent and durable malaria interventions.
Topics: Antibodies, Blocking; Antibodies, Monoclonal; Antibodies, Neutralizing; Antigens, Protozoan; Epitopes; Humans; Malaria Vaccines; Merozoite Surface Protein 1
PubMed: 36202833
DOI: 10.1038/s41467-022-33336-3 -
JCI Insight Jan 2023Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed...
Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.
Topics: Humans; Malaria Vaccines; Antigens, Protozoan; B-Lymphocytes; Lymphocytes; Immunoglobulin G
PubMed: 36692019
DOI: 10.1172/jci.insight.163859 -
Vaccine Dec 2015The Malaria Vaccine Technology Roadmap calls for a 2015 landmark goal of a first-generation malaria vaccine that has protective efficacy against severe disease and... (Review)
Review
The Malaria Vaccine Technology Roadmap calls for a 2015 landmark goal of a first-generation malaria vaccine that has protective efficacy against severe disease and death, lasting longer than one year. This review focuses on product development efforts over the last five years of RTS,S, a pre-erythrocytic, recombinant subunit, adjuvanted, candidate malaria vaccine designed with this goal of a first-generation malaria vaccine in mind. RTS,S recently completed a successful pivotal Phase III safety, efficacy and immunogenicity study. Although vaccine efficacy was found to be modest, a substantial number of cases of clinical malaria were averted over a 3-4 years period, particularly in settings of significant disease burden. European regulators have subsequently adopted a positive opinion under the Article 58 procedure for an indication of active immunization of children aged 6 weeks up to 17 months against malaria caused by Plasmodium falciparum and against hepatitis B. Further evaluations of the benefit, risk, feasibility and cost-effectiveness of RTS,S are now anticipated through policy and financing reviews at the global and national levels.
Topics: Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Drug Discovery; Hepatitis B Surface Antigens; Humans; Immunization Schedule; Immunization, Secondary; Infant; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins; Vaccination; Vaccines, Synthetic
PubMed: 26431982
DOI: 10.1016/j.vaccine.2015.09.061 -
Vaccine May 2021Relapsing malaria caused by Plasmodium vivax is a neglected tropical disease and an important cause of malaria worldwide. Vaccines to prevent clinical disease and...
Relapsing malaria caused by Plasmodium vivax is a neglected tropical disease and an important cause of malaria worldwide. Vaccines to prevent clinical disease and mosquito transmission of vivax malaria are needed to overcome the distinct challenges of this important public health problem. In this vaccine immunogenicity study in mice, we examined key variables of responses to a P. vivax Duffy binding protein vaccine, a leading candidate to prevent the disease-causing blood-stages. Significant sex-dependent differences were observed in B cell (CD80+) and T cell (CD8+) central memory subsets, resulting in significant differences in functional immunogenicity and durability of anti-DBP protective efficacy. These significant sex-dependent differences in inbred mice were in the CD73+CD80+ memory B cell, H2KhiCD38hi/lo, and effector memory subsets. This study highlights sex and immune genes as critical variables that can impact host responses to P. vivax antigens and must be taken into consideration when designing clinical vaccine studies.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Malaria; Malaria Vaccines; Malaria, Vivax; Mice; Plasmodium vivax; Protozoan Proteins
PubMed: 33840564
DOI: 10.1016/j.vaccine.2021.03.072 -
Scientific Reports Aug 2023Toxoplasmosis caused by the opportunistic, cosmopolitan protozoan Toxoplasma gondii is one of the most common parasitoses in the world. Although it may prove dangerous...
Toxoplasmosis caused by the opportunistic, cosmopolitan protozoan Toxoplasma gondii is one of the most common parasitoses in the world. Although it may prove dangerous or even fatal for immunocompromised individuals, immunoprophylaxis for humans is still nonexistent. Thus, the aim of the current work was to assess the ability of two immunogenic recombinant chimeric T. gondii proteins, SAG2-GRA1-ROP1 (SGR) and SAG1-MIC1-MAG1-GRA2 (SMMG), selected in previous experiments to induce long-lasting immunity when administered with a safe adjuvant. Thus, the determination of immunological parameters and parasite challenge were performed both two weeks after the last boost injection and 6 months postvaccination. Both experimental vaccines triggered specific humoral and cellular responses in immunized C3H/HeOuJ male mice, characterized by the production of specific IgG (IgG1/IgG2a) antibodies in vivo and the synthesis of key Th1/Th2 cytokines by Toxoplasma lysate antigen-stimulated splenocytes in vitro. Although the levels of specific antibodies and cytokine release were in most cases lower six months postimmunization, the protection rates conferred by the vaccination were comparable regardless of the time after the administration of the last vaccine dose. The results indicate that both preparations induce long-lasting immunity, which makes them attractive candidates for further research aimed at boosting their immunogenicity and immunoprotective capacity.
Topics: Humans; Animals; Mice; Male; Recombinant Fusion Proteins; Antigens, Protozoan; Protozoan Proteins; Mice, Inbred C3H; Immunization; Vaccination; Toxoplasma; Cytokines; Protozoan Vaccines; Antibodies, Protozoan; Mice, Inbred BALB C
PubMed: 37563166
DOI: 10.1038/s41598-023-40147-z -
The Journal of Parasitology Nov 2021Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of... (Review)
Review
Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of foodborne illness-related death. Currently, there exists no approved vaccine for humans or most livestock against the parasite. DNA vaccines, a type of subunit vaccine which uses segments of the pathogen's DNA to generate immunity, have shown varying degrees of experimental efficacy against infection caused by the parasite. This review compiles DNA vaccine efforts against Toxoplasma gondii, segmenting the analysis by parasite antigen, as well as a review of concomitant adjuvant usage. No single antigenic group was consistently more effective within in vivo trials relative to others.
Topics: Adjuvants, Immunologic; Animals; Antigens, Protozoan; Humans; Microneme; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccines, DNA
PubMed: 34852176
DOI: 10.1645/20-157